CLEVIPREX® (clevidipine) provided blood pressure reduction in a range of patients and various clinical settings


CLEVIPREX vial

Pharmacology: CLEVIPREX rapidly lowers arterial blood pressure

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Titratable, fast onset of action1

In perioperative patients, CLEVIPREX produces a 4%–5% reduction in SBP within 2–4 minutes of initiation. An approximately 1–2 mg/hr increase will generally produce an additional 2–4 mmHg decrease in systolic pressure.


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~1-minute half-life1

CLEVIPREX has a half-life of ~1 minute. In most patients, full recovery of BP is achieved 5–15 minutes after the infusion is stopped.


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Metabolism1

Dosing of CLEVIPREX is independent of hepatic and renal function due to metabolism by plasma and tissue esterases.

The pharmacology of CLEVIPREX

CLEVIPREX is titrated to the desired reduction in BP. The effect of CLEVIPREX appears to plateau at approximately 25% of baseline systolic pressure. The infusion rate for which half the maximal effect is observed is approximately 10 mg/hr.1

Mechanism of action1

CLEVIPREX works by selectively dilating arterial smooth muscle via calcium channel blockade, reducing systemic vascular resistance without affecting preload.

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Efficacy: CLEVIPREX was evaluated across 3 clinical studies

PERIOPERATIVE HYPERTENSION

ESCAPE-12

(N=105):
Efficacy/safety vs placebo preoperatively

PERIOPERATIVE HYPERTENSION

ESCAPE-23

(N=110):
Efficacy/safety vs placebo postoperatively

ACUTE SEVERE HYPERTENSION

VELOCITY4

(N=126):
Open-label efficacy/safety in patients with acute severe hypertension

Responsive BP reduction within minutes in the preoperative clinical setting1-3

92.5% of patients on CLEVIPREX achieved treatment success*

The primary endpoint was the incidence of treatment failure, defined as the inability to decrease SBP by ≥15% from baseline or the discontinuation of study treatment for any reason within the 30-minute period after study drug initiation.2

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Success rate (%) (n=53) (n=52) PLACEBO 0 20 40 60 80 100 92.5 17.3 Treatment success rate* P<0.0001 CLEVIPREX

*Treatment success was defined as a reduction of SBP of ≥15% from baseline within the 30-minute period from study drug initiation.

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Mean change from baseline in SBP (mmHg) CLEVIPREX PLACEBO –50 –40 –30 –20 –10 0 0 5 10 15 20 25 30 Time (minutes) Mean change in SBP (mmHg) during 30-minute infusion 1

Target SBP reduction (≥15% from baseline) achieved with a median time of 6 minutes2

Study type Randomized, double-blind, placebo-controlled study
Purpose To determine the safety and efficacy of clevidipine in treating preoperative hypertension
Patient population
  • N=105
  • Cardiac surgery patients
Key inclusion criteria SBP ≥160 mmHg and clinically assessed as needing ≥15% reduction in SBP
Protocol
  • Initiated CLEVIPREX at 1–2 mg/hr, double dose every ~90 seconds up to 16 mg/hr until desired SBP was achieved. At doses above 16 mg/hr, dose increments were 7 mg/hr
  • Continued treatment for at least 30 minutes, maximum 1 hour, or anesthesia induction

 

Responsive BP reduction within minutes in the postoperative clinical setting1-3

91.8% of patients on CLEVIPREX achieved treatment success*

The primary endpoint was the incidence of treatment failure, defined as the inability to decrease SBP by ≥15% from baseline or the discontinuation of study treatment for any reason within the 30-minute period after study drug initiation.3

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Treatment success rate* Success rate (%) CLEVIPREX (n=61) (n=49) PLACEBO 0 20 40 60 80 100 91.8 20.4 P<0.0001

*Treatment success was defined as a reduction of SBP of ≥15% from baseline within the 30-minute period from study drug initiation.

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Mean change from baseline in SBP (mmHg) –50 –40 –30 –20 –10 0 0 5 10 15 20 25 30 Time (minutes) Mean change in SBP (mmHg) during 30-minute infusion 1 PLACEBO CLEVIPREX

†The decrease in placebo group SBP reflects the number of placebo patients (N=49 at baseline) who bailed out during the 30-minute infusion period (N=10 remaining at 30 minutes).

Target SBP reduction (≥15% from baseline) achieved with a median time of 5.3 minutes3

Study type Randomized, double-blind, placebo-controlled study
Purpose To determine the safety and efficacy of clevidipine in treating postoperative hypertension
Patient population
  • N=110
  • Cardiac surgery patients
Key inclusion criteria SBP ≥140 mmHg and clinically assessed as needing ≥15% reduction in SBP
Protocol
  • Initiated CLEVIPREX at 1–2 mg/hr, double dose every ~90 seconds up to 16 mg/hr until desired SBP was achieved. At doses above 16 mg/hr, dose increments were 7 mg/hr
  • Continued treatment for at least 30 minutes, maximum 1 hour

Control of acute severe hypertension with low rate of overshoot4

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Mean percent change in SBP during the first 30 minutes of infusion in acute severe hypertension 1 Mean PERCENT change from baseline in SBP (%) CLEVIPREX –25 –20 –15 –10 –5 0 0 5 10 15 20 25 30 Time (minutes)
  • Nearly 89% of acute severe hypertension patients achieved target BP4
  • Target SBP range achieved with a median time of 10.9 minutes4
  • No change in lipid profile was observed*4
  • Mean duration of infusion=21 hours1,4

*Increased blood triglycerides have been observed in the postmarketing experience of CLEVIPREX.

VELOCITY safety data

  • Serious adverse events from clevidipine initiation to 7 days later were reported in 11 of 126 (8.7%) safety population patients
  • Headache was the most frequently reported adverse event, with an overall incidence of 6.3% (8/126), followed by nausea 4.8% (6/126), chest discomfort 3.2% (4/126), and vomiting 3.2% (4/126)4
  • The incidence of adverse events leading to study drug discontinuation for CLEVIPREX in severe hypertension was 4.8%

Low rate of overshoot in acute severe hypertension patients4

  • In 1.6% of patients (N=2), SBP decreased below the lower limit of the prespecified initial target range within the first 3 minutes after start of infusion. These 2 patients continued CLEVIPREX infusion beyond 18 hours without experiencing any adverse events
  • In this study, the incidence of adverse events leading to study drug discontinuation was 4.8%1

VELOCITY study design4

An open-label, single-arm clinical trial in 126 patients with severe hypertension (SBP >180 mmHg or DBP >115 mmHg). CLEVIPREX infusion was initiated at 2 mg/hr and up-titrated every 3 minutes, doubling up to a maximum dose of 32 mg/hr as required to achieve a prespecified target blood pressure range within 30 minutes (primary endpoint). The SBP target range was prespecified, patient specific, and calculated as 20–40 mmHg range from upper to lower limit. It was selected by the treating physician’s discretion and according to the patient’s presenting condition, baseline blood pressure, and presence of comorbidities.

Individualized, titratable administration1

CLEVIPREX has a low-volume, non–weight-based dosing regimen that is independent of renal or hepatic function.

50 mL and 100 mL CLEVIPREX single-use vials